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The Rh protein family: gene evolution, membrane biology, and disease association

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Abstract

The Rh (Rhesus) genes encode a family of conserved proteins that share a structural fold of 12 transmembrane helices with members of the major facilitator superfamily. Interest in this family has arisen from the discovery of Rh factor’s involvement in hemolytic disease in the fetus and newborn, and of its homologs widely expressed in epithelial tissues. The Rh factor and Rh-associated glycoprotein (RhAG), with epithelial cousins RhBG and RhCG, form four subgroups conferring upon vertebrates a genealogical commonality. The past decade has heralded significant advances in understanding the phylogenetics, allelic diversity, crystal structure, and biological function of Rh proteins. This review describes recent progress on this family and the molecular insights gleaned from its gene evolution, membrane biology, and disease association. The focus is on its long evolutionary history and surprising structural conservation from prokaryotes to humans, pointing to the importance of its functional role, related to but distinct from ammonium transport proteins.

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Acknowledgments

The authors’ work was supported by NIH grants HL54459, HD62704, and HL66274, and funds from the New York Blood Center. We are grateful to Drs. Olga Blumenfeld for helpful comments, Jason Peng for the expanded analysis of Rh and Amt in Fig. 3b, and Michael Chan and Xin Li for Fig. 5. We thank Drs. Sydney Kustu, Michael Chan, and Jonathan Kaunitz for preprints and personal communications. We also want to express our gratitude to Dr. Mohandas Narla for support and interest in the Rh topics.

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  1. Laboratory of Biochemistry and Molecular Genetics, Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street, New York, NY, 10065, USA

    Cheng-Han Huang & Mao Ye

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Correspondence to Cheng-Han Huang.

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Huang, CH., Ye, M. The Rh protein family: gene evolution, membrane biology, and disease association. Cell. Mol. Life Sci. 67, 1203–1218 (2010). https://doi.org/10.1007/s00018-009-0217-x

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